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  • #174 Integrated multi-omic and clinicopathological analysis of vulvar squamous cell carcinoma: identification of predictive biomarkers for personalized treatment

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Poster/ePoster Sessions
11. Translational Research/Biomarkers
#174 Integrated multi-omic and clinicopathological analysis of vulvar squamous cell carcinoma: identification of predictive biomarkers for personalized treatment
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  1. Tibor A Zwimpfer1,2,
  2. Flavio Lombardo3,
  3. Natalie Rimmer3,
  4. Sandra Götze4,
  5. Franziska Singer4,
  6. Anne Bertolini4,
  7. Céline Montavon1,
  8. Christian Kurzeder1,
  9. Francis Jacob3 and
  10. Viola Heinzelmann-Schwarz1
  1. 1University Hospital Basel, Gynecological Oncology, Basel, Switzerland
  2. 2Peter MacCallum Cancer Centre, Cancer Research, Melbourne, Australia
  3. 3University Hospital and University Basel, Department of Biomedicine, Basel, Switzerland
  4. 4ETH Zürich, NEXUS Personalized Health Technologies, Zürich, Switzerland. SIB Swiss Institute of Bioinformatics, Zuerich, Switzerland

Abstract

Introduction/Background Vulvar cancer responds poorly to systemic treatment and in contrast to other gynecological cancers, targeted therapies remain at an early stage. Interactions of clinical, immune, and molecular biomarkers remain poorly understood for this rare cancer type. Here, we characterized the proteogenome of vulvar squamous cell carcinoma (vSCC) and provide a computational workflow to integrate publicly available data to study this rare and aggressive cancer type.

Methodology Whole exome sequencing, bulk RNA-sequencing, clinicopathological, and proteomics data from 23 patients with vSCC were analyzed. In addition, a total of 5543 women-derived TCGA genomic and transcriptomics sequencing data were obtained for this analysis.

Results Our cohort consisted of 34.8% human papillomavirus (HPV)+ and 65.2% HPV- vSCC patients. Early FIGO stage was significantly associated with HPV- status (12% (1/8) vs. 86% (12/15), p<0.001). TP53 and CDKN2 were mutually exclusive to HPV+. Patients being HPV+ revealed a higher frequency in PIK3CA alterations with 37.5% vs. 6.7% in HPV-. TYMS which is considered the primary site of action for 5-fluorouracil was significantly higher expressed in HPV+ patients (log2FC=1.7497, p<0.001). We identified unique single and doublet base substitution signatures in vSCC indicating defective DNA mismatch-repair and correlation with age. Tongue SCC (tSCC) was identified as a comparison cohort supported by different clustering methods of conjoint RNA-seq and clinicopathological data, derived from TCGA. vSCC was associated with elevated activated mast cells (p=0.0031), monocytes (p=0.0027), and M2 macrophages (p<0.001) compared to tSCC, independent of the HPV status.

Conclusion vSCC can be further distinguished by HPV status, somatic gene alterations and tumour microenvironment, while a similar cancer tissue has been identified with tSCC. Further analysis is targeted at identifying molecular signatures serving as biomarkers in vSCC and to suggest alternative treatment options of drugs already in use in tSCC or other cancer types.

Disclosures All authors declare that they have no conflicts of interest.

https://doi.org/10.1136/ijgc-2023-ESGO.773

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